Examining how stress affects brain blood flow differently in men and women

Human Cerebral Blood Flow Regulation: Sex, Mechanism, and Stress Differences (Phase 2)

This study is testing how stress affects blood flow in the brain differently for men and women by looking at healthy young adults and using advanced MRI techniques.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years to 40 Years
• Sex: All
• Sponsor: University of Wisconsin, Madison (other)
• Locations: 1 site (Madison, Wisconsin)
• Trial ID: NCT06253702 on ClinicalTrials.gov

What this trial studies

This study investigates the influence of sex and sex hormones on cerebral blood flow (CBF) control in healthy young adults aged 18-40. It aims to determine whether men and women exhibit different responses in CBF to physiological stressors and to identify the underlying mechanisms that regulate these responses. Participants will undergo CBF testing using advanced MRI techniques, with specific interventions including indomethacin, placebo, or hormonal treatments. The study will last approximately 16 days and will include both hypoxia and hypercapnia trials to assess CBF responses.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18-40, both male and female, who have completed a prior related study.

Not a fit: Patients with a history of cerebrovascular disease or other significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new sex-specific therapeutic options for cerebrovascular disorders.

How similar studies have performed: While this study explores a novel approach, previous studies have indicated sex differences in cerebrovascular responses, suggesting potential for meaningful insights.

Eligibility criteria

Inclusion Criteria:

* Age between ≥18 - ≤40 years inclusive
* Completed Phase 1: Study 2020-0336

Exclusion Criteria:

* Hypertensive

  * \> 125 mmHg systolic blood pressure; or
  * \> 80 mmHg diastolic blood pressure
* BMI ≥25 kg/m2
* Fasting blood glucose ≥100 mg/dl
* LDL cholesterol ≥130 mg/dl
* Triglycerides ≥150 mg/dl
* Current diagnosis or history of:

  * peripheral vascular disease
  * hepatic disease
  * renal disease
  * lung disease
  * gastrointestinal disorders/bleeding
  * hematologic disease
  * stroke
  * myocardial infarction
  * coronary heart disease
  * congestive heart failure
  * heart surgery
  * prediabetes
  * diabetes mellitus (type 1, type 2, MODY, or others)
  * sleep apnea
  * hypertension
  * some autoimmune diseases, such as inflammatory bowel disease or systemic lupus erythematosus (exclusion at discretion of reviewing MD)
* Current smoking, defined as the use of tobacco or nicotine products \>5 times in the past 30 days.
* Cardiovascular medication use
* NSAID sensitivity
* Magnesium-restricted diet
* Any contraindications of having an MRI

  * (e.g. the requirement of anxiolytics in order to complete an MRI scan)
* Irregular menstrual cycle (females only)
* Medical conditions that can affect the menstrual cycle, such as hyperprolactinemia, prolactinoma, hypercortisolemia, and congenital adrenal hyperplasia (females only)
* Pregnancy, breast feeding, or plans to conceive within the next 3 months (females only)
* Polycystic ovary syndrome (females only)
* Hirsutism defined as unwanted and/or excessive hair growth on the face, chest, or back (females only)
* Levonorgestrel intrauterine device (IUD) (females only)
* Hormonal birth control will not be allowed in women, in order to control for high variability between type, dose, and route of therapy. However, in discussion with Dr. Davis (Co-I) and Dr. Laura Cooney M.D., physician experts in medical and reproductive endocrinology and infertility, there are two broad exceptions to this birth control criteria:

  * Copper intrauterine devices (IUDs) will be allowed as they do not change systemic sex hormone levels).
  * Women currently taking hormonal birth control (i.e. contraceptive pills, patch, ring) for contraception only (not for a medical condition such as those listed in exclusion criteria above) may consider temporarily stopping to become eligible for enrollment. Hormonal birth control must be stopped at least one month prior to Study Visit 1 to provide time for menstruation to resume. Then stoppage continues through the last planned study visit. Screening information will be reviewed by endocrinology physicians to determine eligibility and timing on this issue.

Where this trial is running

Madison, Wisconsin

• University of Wisconsin — Madison, Wisconsin, United States (RECRUITING)

Study contacts

• Principal investigator: William G Schrage, PhD — University of Wisconsin, Madison
• Study coordinator: Shawn Bolin, MS

Conditions: Cerebrovascular Disorders